Hyperbaric Oxygen Effects on Persistent Post-concussive Symptoms

NCT ID: NCT05173818

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-28

Study Completion Date

2025-08-01

Brief Summary

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Persistent post-concussive symptoms (PPCS) are a source of significant burden among a subset of patients with concussion with prevalence rates previously reported between 11 - 82% based on timing of assessment, diagnostic criteria, or population under study.

Examples of persistent post-concussion symptoms include balance problems, headaches, fatigue, poor concentration, forgetfulness, anxiety, irritability, and sleep disturbance. Few proposed therapies have proved successful in the management of persistent post-concussion symptoms following mild traumatic brain injury.

The investigators will explore hyperbaric oxygen administered in a randomized sham-controlled clinical trial as an effective and tolerable treatment in improving neuropsychological status among adult patients with persistent post-concussive symptoms.

The overall hypothesis to be evaluated is that hyperbaric oxygen improves neuropsychological status and a serum concussion biomarker associated with PPCS.

Detailed Description

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This is a parallel, randomized, double-blinded and sham-controlled study. A total of 100 subjects will be randomly assigned to either an intervention arm: 50 participants exposed to \> 99.9% oxygen at 1.5 atmosphere absolute for 60 minutes over 40 treatments or sham-treatment arm: 50 participants exposed to oxygen and pressure composition equivalent to breathing atmospheric air for 60 minutes over 40 treatments.

This study is designed to determine whether hyperbaric oxygen improves neuropsychological status and ameliorates symptoms in adults with persistent post-concussive symptoms (PPCS) following mild traumatic brain injury. It recruits from either military or civilian population; uses a validated screening tool - Repeatable battery for the assessment of neuropsychological status (RBANS)- used in dementia and other forms of brain injury not used hitherto, in previous randomized control trial that investigated the effectiveness of hyperbaric oxygen in the management of PPCS. It also includes a concssuon biomarker, as an objective secondary endpoint.

The study is based on repeated measure design. The study will describe and track changes in the outcomes of interest over time, and examine associations between measures within each participant and across certain participant characteristics.

Conditions

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Persistent Post-concussive Syndrome Concussion Post Syndrome

Keywords

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Hyperbaric oxygen treatment Neurofilament light chain RBANS

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel Assignment
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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HBO at 1.5 Atmosphere absolute

Participants in this group will be exposed to hyperbaric oxygen at 1.5 atmosphere absolute (ATA) for 60 minutes per session. Each participant will complete 40 sessions, five sessions per week within 3 months from randomization

Group Type EXPERIMENTAL

Hyperbaric oxygen at 1.5 ATA

Intervention Type DRUG

Hyperbaric oxygen (HBO2) at 1.5 ATA (active) group (hyperbaric oxygen-chamber compressed to 1.5 atmosphere absolute and breathing \>99.9% oxygen). Each participant should complete 40 sessions, one session per day, five per week over the course of 3 months.

Sham control initially at 1.2 then changed to 1.0 ATA

Participants in this group will be exposed to hyperbaric oxygen at 1.2 atmosphere absolute (ATA) during the first 5 to 7 minutes and the chamber pressure will be reduced to 1.0 ATA for the remaining 53 - 57 minutes for a total of 60 minutes per session. Each participant will complete 40 sessions, five sessions per week within 3 months from randomization

Group Type SHAM_COMPARATOR

Sham treatment

Intervention Type DRUG

Sham treatment includes pressurizing the chamber to 1.2 ATA with air for 5 minutes with noise of circulating air, return the chamber to 1.0 ATA after 5-7 minutes and maintain it at that pressure for until the end of the treatment, with noise of circulating air. Internal control knobs will be concealed. Participants will be instructed to undergo intermittent ear clearing technique during the initial 5 minutes of "descent"

Interventions

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Hyperbaric oxygen at 1.5 ATA

Hyperbaric oxygen (HBO2) at 1.5 ATA (active) group (hyperbaric oxygen-chamber compressed to 1.5 atmosphere absolute and breathing \>99.9% oxygen). Each participant should complete 40 sessions, one session per day, five per week over the course of 3 months.

Intervention Type DRUG

Sham treatment

Sham treatment includes pressurizing the chamber to 1.2 ATA with air for 5 minutes with noise of circulating air, return the chamber to 1.0 ATA after 5-7 minutes and maintain it at that pressure for until the end of the treatment, with noise of circulating air. Internal control knobs will be concealed. Participants will be instructed to undergo intermittent ear clearing technique during the initial 5 minutes of "descent"

Intervention Type DRUG

Other Intervention Names

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1.5 ATA 1.2 ATA then changed to 1.0 ATA

Eligibility Criteria

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Inclusion Criteria

* Volunteers must have a history of mild traumatic brain injury, specifically, persistent post-concussive symptoms after examination by a neuropsychologist or neurologist.
* Volunteers time from concussive incident (Mild traumatic brain injury) must be between 3 months - 5 years following head trauma incident
* TBI was caused by non-penetrating trauma
* Volunteers must have current complaints of TBI symptoms such as headache, dizziness, or cognitive or affective problems
* Volunteers must be 18-year-old or more
* Willing and able to provide informed consent
* Able to speak and read English, as primary language
* Agrees to provide blood samples for clinical lab tests
* Willing and committed to comply with research protocol and complete all outcome measures
* Able to equalize middle ear pressures or willing to undergo needle myringotomies if needed
* Willingness and committed to comply with study protocol outlined reproductive plan based on baseline reproductive status

Exclusion Criteria

* Prior treatment with hyperbaric oxygen treatment
* Hyperbaric chamber inside attendant, professional, SCUBA diver (technical, commercial, operational/military or recreational)
* The investigators will exclude pregnant women from this study because potential fetal adverse reactions triggered by high oxygen partial pressures such as retrolenticular fibroplasia though careful review of human data are generally reassuring such as the use of hyperbaric oxygen to treat acute carbon monoxide poison in the pregnant patient.13
* Prisoners
* Minors
* Unable to protect airway or requires frequent suctioning
* Known or suspected peri-lymphatic fistula
* Presence of tracheostomy (due to limitations in auto-inflating the middle ear)
* Unable to participate fully in outcome assessments
* Unable to cooperate with hyperbaric oxygen treatments
* Unable to speak and read English, as primary language
* Not cooperating with instructions during hyperbaric oxygen treatments such as bringing contraband items into the chamber (such as fire lighter)
* Not competent to sign their own consent. Such potential participants will not have the capacity to participate in a full range of neurocognitive testing
* Pre-existing diagnosis of a psychotic disorder(s): schizophrenia, bipolar, dissociative disorder
* History of moderate or severe traumatic brain injury
* History of brain injury not of traumatic etiology such as stroke or drug-induced coma
* Verifiable diagnosis of learning disability. Other pre-existing cognitive issues may make it difficult for potential participants to fill out certain outcome assessments such as neurobehavioral symptomatic inventory. This could lead to measurement bias or confound the result.
* Claustrophobia and unwilling to enter hyperbaric chamber
* Untreated pneumothorax
* Presence of implanted device with un-verifiable test to pressure by manufacturer
* Concurrent enrollment in an alternate interventional trial for post concussive symptoms
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of North Dakota

OTHER

Sponsor Role collaborator

Dakota Medical Foundation

UNKNOWN

Sponsor Role collaborator

The Swanson Foundation

UNKNOWN

Sponsor Role collaborator

State of North Dakota

UNKNOWN

Sponsor Role collaborator

Essentia Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olayinka D Ajayi, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Essentia Health

Marc Basson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Dakota

Marilyn Klug, PhD

Role: STUDY_CHAIR

University of North Dakota

Paulina Kunecka, MD

Role: STUDY_CHAIR

Essentia Health

Richard Ferraro, PhD

Role: STUDY_CHAIR

University of North Dakota

Rebecca Quinn, MSW, LMSW

Role: STUDY_CHAIR

Center for Rural Health, University of North Dakota

Sharon Hanson, RN

Role: STUDY_DIRECTOR

Essentia Health

Locations

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Essentia Health

Fargo, North Dakota, United States

Site Status

Countries

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United States

References

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Moser RS, Schatz P. Enduring effects of concussion in youth athletes. Arch Clin Neuropsychol. 2002 Jan;17(1):91-100.

Reference Type BACKGROUND
PMID: 14589756 (View on PubMed)

Shahim P, Politis A, van der Merwe A, Moore B, Chou YY, Pham DL, Butman JA, Diaz-Arrastia R, Gill JM, Brody DL, Zetterberg H, Blennow K, Chan L. Neurofilament light as a biomarker in traumatic brain injury. Neurology. 2020 Aug 11;95(6):e610-e622. doi: 10.1212/WNL.0000000000009983. Epub 2020 Jul 8.

Reference Type BACKGROUND
PMID: 32641538 (View on PubMed)

Cook PA, Johnson TM, Martin SG, Gehrman PR, Bhatnagar S, Gee JC. A Retrospective Study of Predictors of Return to Duty versus Medical Retirement in an Active Duty Military Population with Blast-Related Mild Traumatic Brain Injury. J Neurotrauma. 2018 Apr 15;35(8):991-1002. doi: 10.1089/neu.2017.5141. Epub 2018 Mar 1.

Reference Type BACKGROUND
PMID: 29239267 (View on PubMed)

Weaver LK, Wilson SH, Lindblad AS, Churchill S, Deru K, Price RC, Williams CS, Orrison WW, Walker JM, Meehan A, Mirow S. Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial. Undersea Hyperb Med. 2018 Mar-Apr;45(2):129-156.

Reference Type RESULT
PMID: 29734566 (View on PubMed)

Other Identifiers

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EH21714

Identifier Type: -

Identifier Source: org_study_id